For over a century, the traditional method of stimulating neural activity in humans during medical procedures has been based on electrical methods, which has undergone few modifications over the years and remains the gold standards to date. Electrical stimulation is utilized to identify the connectivity and functionality of specific nerve roots to be selectively avoided or resected as well as to create a unique map of functional structures that varies among individuals during brain tumor resection. However, electrical stimulation is prone to electrical interference from the environment, high frequency artifacts associated with the electrical signal used, intrinsic damage caused by the electrodes used for stimulation themselves, population response due to the recruitment of multiple axons, which prevents simultaneous stimulation and recording of adjacent areas, and in general poor spatial specificity.
Alternative approaches exist for stimulation of neural fibers (tissues) by optical irradiation. Researches on the excitability of neural tissue as a by-product of laser therapies and the capability of light in modulating its electrical conductivity have been reported [1, 2].
The use of lasers in medical procedures can be grouped into two distinct categories, therapeutic and diagnostic or imaging applications. In therapeutic procedures, the interaction between the laser and biological tissue results in a light distribution and absorption and subsequent photobiological effect that can be classified into, at least, three mechanistic categories, (1) photochemical, (2) photothermal, and (3) photomechanical [3]. Action potential propagation in neurons through chemical, thermal, and mechanical means [4-6] have been demonstrated. Photochemical effects depend on the absorption of light to act as a reagent in a stoichiometric reaction catalyzed by some photosensitizer. An example of a photochemical effect is the production of reactive chemicals (ultimately leading to oxygen radicals) reported in photodynamic therapy (PDT) by the combination of an injected extrinsic dye, singlet oxygen, and light [7-9]. Frequently, biostimulation is also attributed to photochemical interactions thought to target natural intrinsic agents, although this is not scientifically ascertained [10, 11]. Photothermal effects result from the transformation of absorbed light energy to heat, which may lead to hyperthermia, coagulation, or ablation of the target tissue [12]. Photomechanical effects are secondary to rapid heating with short laser pulses (<1 μs) that produce mechanical forces, such as explosive events and laser-induced pressure waves able to disturb cells and tissue [13, 14]. This classification of laser tissue interactions can be further separated into three distinct categories including; thermoelastic expansion, ablative recoil, and expansion secondary to phase change [15].
In the majority of therapeutic laser applications, the laser-tissue interaction is mediated by a thermal or thermo-mechanical process depending on the operational parameters of the laser, such as wavelength (λ), pulse duration (τ), and laser radiant exposure or irradiance. In general, the objective is to damage tissue locally by exploiting high spatial precision and the ability to couple laser light into fiber optics for minimally invasive delivery to the tissue [16]. While optical nerve stimulation does exploit these distinctive delivery advantages, the therapeutic result for this technique is a stimulation effect in tissue rather than destruction. Laser radiant exposure (J/cm2) associated with these procedures results in either reversible or non-reversible thermal or mechanical alterations of the tissue. The key parameter, wavelength, determines light distribution in the tissue dictated by wavelength dependent optical properties. The energy density and subsequent temperature rise resulting from absorption of optical energy is inversely proportional to the penetration depth and depending on the laser radiant exposure, a temperature increase is induced in the tissue (for comprehensive review see: [17]). While photochemical processes are often governed by a specific reaction pathway, photothermal effects are non-specific and are mediated by absorption of optical energy and secondly governed by fundamental principles of heat transport. Subsequent effects in the target tissue are determined by the temperature rise and the duration of the temperature exposure as described by an Arrhenius rate process [18].
It is important to point out that the duration of the laser exposure, which is largely similar to the interaction time itself, distinguishes and primarily controls these photobiological processes. According to a graph of the laser radiant exposure versus the duration of pulse width the time scale can roughly be divided in three major sections [3]; continuous wave or exposure times >1 s for photochemical interactions, 100 s down to 1 μs for photothermal interactions, and 1 μs and shorter for photomechanical interactions, as shown in FIG. 10. These boundaries are not strict and adjacent interaction types cannot always be separated. For example, in the range of 1 μs to several hundreds of μs, the interaction mechanism has photothermal as well as photomechanical components, while many photochemical interactions also exhibit photothermal components.
Great clinical relevance would be gained if optimal laser parameters for safe and effective stimulation of nerves could be determined from the laser-tissue interactions that occur during optical nerve stimulation in clinical implementations. Understanding the biophysical mechanism will ultimately help to refine an optimal laser parameter set to effectively target the diverse morphology of neural tissue types as well as identify possible clinical applications and limitations for this nerve stimulation modality.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.